Exacerbated inflammatory cellular immune response characteristics of HAM/TSP is observed in a large proportion of HTLV-I asymptomatic carriers

BACKGROUND: A small fraction of Human T cell Leukemia Virus type-1 (HTLV-I) infected subjects develop a severe form of myelopathy. It has been established that patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) show an exaggerated immune response when compared with the immunological response observed in HTLV-I asymptomatic carriers. In this study the immunological responses in HAM/TSP patients and in HTLV-I asymptomatic carriers were compared using several immunological assays to identify immunological markers associated with progression from infection to disease. METHODS: Immunoproliferation assays, cytokine levels of unstimulated cultures, and flow cytometry analysis were used to evaluate the studied groups. Nonparametric tests (Mann-Whitney U test and Wilcoxon matched-pairs signed ranks) were used to compare the difference between the groups. RESULTS: Although both groups showed great variability, HAM/TSP patients had higher spontaneous lymphoproliferation as well as higher IFN-γ levels in unstimulated supernatants when compared with asymptomatic carriers. Flow cytometry studies demonstrated a high frequency of inflammatory cytokine (IFN-γ and TNF-α) producing lymphocytes in HAM/TSP as compared to the asymptomatic group. This difference was accounted for mainly by an increase in CD8 cell production of these cytokines. Moreover, the HAM/TSP patients also expressed an increased frequency of CD28-/CD8+ T cells. Since forty percent of the asymptomatic carriers had spontaneous lymphoproliferation and IFN-γ production similar to HAM/TSP patients, IFN-γ levels were measured eight months after the first evaluation in some of these patients to observe if this was a transient or a persistent situation. No significant difference was observed between the means of IFN-γ levels in the first and second evaluation. CONCLUSIONS: The finding that a large proportion of HTLV-I carriers present similar immunological responses to those observed in HAM/TSP, strongly argues for further studies to evaluate these parameters as markers of HAM/TSP progression

Cannabinoid Agonists Inhibit Neuropathic Pain Induced by Brachial Plexus Avulsion in Mice by Affecting Glial Cells and MAP Kinases

Many studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.Mice underwent BPA or sham surgery. The mRNA levels and protein expression of CB(1) and CB(2) receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5(th) and 30(th) days after surgery. We observed a marked increase in CB(1) and CB(2) receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5(th) or 30(th) day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30(th) day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5(th) and 30(th) days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5(th) and 30(th) days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30(th) day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.Our results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection.

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses.Defense Advanced Research Projects AgencyArmy Research Office through Grant W911NF-15-1-010

Disparidade urbano-rural na utilização de serviços de saúde em município de pequeno porte

Objective: to analyze the existence of urban-rural disparity in health services utilization by people living in a small municipality. Methods: cross-sectional study with a representative random sample of people aged 18 years and older in the urban area (n=1.235) and the entire population of a rural district (n=190). The Health Services Utilization questionnaire, from the National Household Survey in Brazil, was used. The analysis considered logistic regression models to examine factors associated with health services utilization within 30 days prior to the study. Results: the utilization rate by people in urban area was significantly higher than in rural area (45.0% vs 15.8%). Women and people who reported symptoms of diseases and diagnosis of hypertension were more likely to use health services. Conclusion: under the same municipal health organization, people living in the rural area have lower health services utilization when compared to those living in the urban area.Objetivo: analisar a existência de disparidade urbano-rural na utilização de serviços de saúde por pessoas vivendo em um município de pequeno porte. Métodos: estudo epidemiológico transversal com amostra representativa e aleatória de pessoas com 18 anos ou mais de idade na área urbana (n=1.235) e toda a população de um distrito rural (n=190). Utilizou-se o questionário sobre utilização de serviços da Pesquisa Nacional por Amostra de Domicílios. A análise considerou modelos de regressão logística para examinar fatores associados à utilização nos 30 dias anteriores ao estudo. Resultados: a taxa de utilização pelas pessoas da área urbana foi significativamente maior que da área rural (45,0% vs 15,8%). Mulheres e aqueles que reportaram sintomas de doenças no período e hipertensão arterial tiveram mais chances de utilização. Conclusão: pessoas residentes em área rural utilizam menos serviços de saúde quando comparadas àquelas da área urbana quando estão sob a mesma organização municipal de saúde